Treatment of Streptococcal Endocarditis with a Single Daily Dose of Ceftriaxone and Netilmicin for 14 Days: A Prospective Multicenter Study

A 2-week course of ceftriaxone (2 g) plus netilmicin (4 mglkg), administered as one short daily iv infusion, was evaluated for the treatment of streptococcal endocarditis in an open multicenter study. Of the 52 patients, 31 were infected with viridans streptococci, 18 with Streptococcus bovis, two with Gemella morbillorum, and one with group C Streptococcus; 48 patients were assessable. Infection was cured in 42 cases, 35 treated medically and seven treated both medically and surgically. Five patients died without evidence of active infection, and one relapsed. The bacteriologic failure was due to a strain of G. morbillorum against which no synergy of ceftriaxone and netilmicin was evident in vitro. The serum creatinine level increased during treatment in four cases, all involving patients >65 years old who had renal risk factors; in two of these cases, values did not return to baseline during follow-up. Of 40 patients assessed for auditory function, only one developed decreased perception of borderline significance. Other adverse reactions were mild. This regimen was efficacious, safe, and cost-effective for the treatment of streptococcal endocarditis. However, it must be used with caution for patients with preexisting renal impairment or concomitant exposure to other potentially nephrotoxic agent

Infecciones intraabdominales

En los últimos años se ha incrementado el interés por las infecciones intraabdominales como consecuencia del avance en el conocimiento de la etiopatogenia de las infecciones intraabdominales, el desarrollo de nuevos métodos diagnósticos no invasivos (Tomografía Computada, Centellografía, Ecografía) y la aparición de nuevos antimicrobianos. A pesar de estos hechos, estas infecciones siguen teniendo una gran morbimortalidad y lo fundamental para mejorar su pronóstico continúa siendo el diagnóstico precoz preciso del tipo de infección y la apliación oportuna del tratamiento quirúrgico. Es nuestro objetivo a través de esta breve publicación enfatizar algunos aspectos salientes relacionados con la incidencia, evolución y pronóstico de algunas formas clínicas; el diagnóstico por imágenes, y el tratamiento antimicrobiano y la profilaxis antibiótica en la cirugía abdominal. Incluimos en este trabajo, además, referencias bibliográficas publicadas en los últimos años sobre el tema.Facultad de Ciencias Médica

Infecciones intraabdominales

En los últimos años se ha incrementado el interés por las infecciones intraabdominales como consecuencia del avance en el conocimiento de la etiopatogenia de las infecciones intraabdominales, el desarrollo de nuevos métodos diagnósticos no invasivos (Tomografía Computada, Centellografía, Ecografía) y la aparición de nuevos antimicrobianos. A pesar de estos hechos, estas infecciones siguen teniendo una gran morbimortalidad y lo fundamental para mejorar su pronóstico continúa siendo el diagnóstico precoz preciso del tipo de infección y la apliación oportuna del tratamiento quirúrgico. Es nuestro objetivo a través de esta breve publicación enfatizar algunos aspectos salientes relacionados con la incidencia, evolución y pronóstico de algunas formas clínicas; el diagnóstico por imágenes, y el tratamiento antimicrobiano y la profilaxis antibiótica en la cirugía abdominal. Incluimos en este trabajo, además, referencias bibliográficas publicadas en los últimos años sobre el tema.Facultad de Ciencias Médica

Infecciones intraabdominales

En los últimos años se ha incrementado el interés por las infecciones intraabdominales como consecuencia del avance en el conocimiento de la etiopatogenia de las infecciones intraabdominales, el desarrollo de nuevos métodos diagnósticos no invasivos (Tomografía Computada, Centellografía, Ecografía) y la aparición de nuevos antimicrobianos. A pesar de estos hechos, estas infecciones siguen teniendo una gran morbimortalidad y lo fundamental para mejorar su pronóstico continúa siendo el diagnóstico precoz preciso del tipo de infección y la apliación oportuna del tratamiento quirúrgico. Es nuestro objetivo a través de esta breve publicación enfatizar algunos aspectos salientes relacionados con la incidencia, evolución y pronóstico de algunas formas clínicas; el diagnóstico por imágenes, y el tratamiento antimicrobiano y la profilaxis antibiótica en la cirugía abdominal. Incluimos en este trabajo, además, referencias bibliográficas publicadas en los últimos años sobre el tema.Facultad de Ciencias Médica

Threshold-Free Population Analysis Identifies Larger DRG Neurons to Respond Stronger to NGF Stimulation

Sensory neurons in dorsal root ganglia (DRG) are highly heterogeneous in terms of cell size, protein expression, and signaling activity. To analyze their heterogeneity, threshold-based methods are commonly used, which often yield highly variable results due to the subjectivity of the individual investigator. In this work, we introduce a threshold-free analysis approach for sparse and highly heterogeneous datasets obtained from cultures of sensory neurons. This approach is based on population estimates and completely free of investigator-set parameters. With a quantitative automated microscope we measured the signaling state of single DRG neurons by immunofluorescently labeling phosphorylated, i.e., activated Erk1/2. The population density of sensory neurons with and without pain-sensitizing nerve growth factor (NGF) treatment was estimated using a kernel density estimator (KDE). By subtraction of both densities and integration of the positive part, a robust estimate for the size of the responsive subpopulations was obtained. To assure sufficiently large datasets, we determined the number of cells required for reliable estimates using a bootstrapping approach. The proposed methods were employed to analyze response kinetics and response amplitude of DRG neurons after NGF stimulation. We thereby determined the portion of NGF responsive cells on a true population basis. The analysis of the dose dependent NGF response unraveled a biphasic behavior, while the study of its time dependence showed a rapid response, which approached a steady state after less than five minutes. Analyzing two parameter correlations, we found that not only the number of responsive small-sized neurons exceeds the number of responsive large-sized neurons—which is commonly reported and could be explained by the excess of small-sized cells—but also the probability that small-sized cells respond to NGF is higher. In contrast, medium-sized and large-sized neurons showed a larger response amplitude in their mean Erk1/2 activity

Identification of calcium-binding proteins associated with the human sperm plasma membrane

<p>Abstract</p> <p>Background</p> <p>The precise composition of the human sperm plasma membrane, the molecular interactions that define domain specific functions, and the regulation of membrane associated proteins during the capacitation process, still remain to be fully understood. Here, we investigated the repertoire of calcium-regulated proteins associated with the human sperm plasma membrane.</p> <p>Methods</p> <p>Surface specific radioiodination was combined with two-dimensional gel electrophoresis, a 45Ca-overlay assay, computer assisted image analysis and mass spectrometry to identify calcium-binding proteins exposed on the human sperm surface.</p> <p>Results</p> <p>Nine acidic 45Ca-binding sperm proteins were excised from stained preparative 2D gels and identified by mass spectrometry. Five of the calcium binding proteins; HSPA2 (HSP70-1), HSPA5 (Bip), HYOU1 (ORP150), serum amyloid P-component (SAP) and protein kinase C substrate 80K-H (80K-H) were found to be accessible to Iodo-Bead catalyzed 125I-labelling on the surface of intact human sperm. Agglutination and immunofluorescence analysis confirmed that SAP is situated on the plasma membrane of intact, motile sperm as well as permeabilized cells. Western blot analysis showed increased phosphorylation of human sperm 80K-H protein following in vitro capacitation. This is the first demonstration of the 80K-H protein in a mammalian sperm.</p> <p>Conclusion</p> <p>The presence of SAP on the surface of mature sperm implies that SAP has a physiological role in reproduction, which is thought to be in the removal of spermatozoa from the female genital tract via phagocytosis. Since 80K-H is a Ca2+-sensor recently implicated in the regulation of both inositol 1,4,5-trisphosphate receptor and transient receptor potential (TRP) cation channel activities, its detection in sperm represents the first direct signaling link between PKC and store-operated calcium channels identified in human sperm.</p

Post-translational modifications of voltage-gated sodium channels in chronic pain syndromes.

In the peripheral sensory nervous system the neuronal expression of voltage-gated sodium channels (Navs) is very important for the transmission of nociceptive information since they give rise to the upstroke of the action potential (AP). Navs are composed of nine different isoforms with distinct biophysical properties. Studying the mutations associated with the increase or absence of pain sensitivity in humans, as well as other expression studies, have highlighted Nav1.7, Nav1.8, and Nav1.9 as being the most important contributors to the control of nociceptive neuronal electrogenesis. Modulating their expression and/or function can impact the shape of the AP and consequently modify nociceptive transmission, a process that is observed in persistent pain conditions. Post-translational modification (PTM) of Navs is a well-known process that modifies their expression and function. In chronic pain syndromes, the release of inflammatory molecules into the direct environment of dorsal root ganglia (DRG) sensory neurons leads to an abnormal activation of enzymes that induce Navs PTM. The addition of small molecules, i.e., peptides, phosphoryl groups, ubiquitin moieties and/or carbohydrates, can modify the function of Navs in two different ways: via direct physical interference with Nav gating, or via the control of Nav trafficking. Both mechanisms have a profound impact on neuronal excitability. In this review we will discuss the role of Protein Kinase A, B, and C, Mitogen Activated Protein Kinases and Ca++/Calmodulin-dependent Kinase II in peripheral chronic pain syndromes. We will also discuss more recent findings that the ubiquitination of Nav1.7 by Nedd4-2 and the effect of methylglyoxal on Nav1.8 are also implicated in the development of experimental neuropathic pain. We will address the potential roles of other PTMs in chronic pain and highlight the need for further investigation of PTMs of Navs in order to develop new pharmacological tools to alleviate pain